The subject invention relates, generally, to methods and materials for protecting a subject against myocardial cell damage and, more particularly, for protecting a subject against myocardial cell damage resulting from coronary intervention.
Percutaneous coronary intervention (xe2x80x9cPCIxe2x80x9d) is an important treatment for coronary artery disease and other forms of atherosclerosis obstruction of the coronary arteries. However, myocardial necrosis (infarction) during PCI may occur in almost half of otherwise successful PCI (Klein et al., xe2x80x9cIncidence and Clinical Significance of Transient Creatine Kinase Elevations and the Diagnosis of Non-Q Wave Myocardial Infarction Associated with Coronary Angioplasty,xe2x80x9d J. Am. Coll. Cardiol., 17:621-626 (1991) (xe2x80x9cKleinxe2x80x9d); Oh et al., xe2x80x9cCreatine Kinase Release after Successful Percutaneous Transluminal Coronary Angioplasty,xe2x80x9d Am. Heart J., 109:1225-1231 (1985) (xe2x80x9cOhxe2x80x9d); and Pauletto et al., xe2x80x9cChanges in Myoglobin, Creatine Kinase, and Creatine Kinase-MB after Percutaneous Transluminal Coronary Angioplasty for Stable Angina Pectoris,xe2x80x9d Am. J. Cardiol., 59: 999-1000 (1987)) and is associated with an increased incidence of late adverse outcomes, particularly death, even with minor elevations in biochemical markers (Simoons et al., xe2x80x9cMinimal myocardial damage during coronary intervention is associated with impaired outcome,xe2x80x9d Eur. Heart J., 20:1112-1119 (1999) (xe2x80x9cSimoonsxe2x80x9d); Kong et al., xe2x80x9cPrognostic implication of creatine kinase elevation following elective coronary artery interventions,xe2x80x9d JAMA, 277:461-466 (1997); Abdelmeguid et al., xe2x80x9cSignificance of Mild Transient Release of Creatine Kinase-MB Fraction after Percutaneous Coronary Interventions,xe2x80x9d Circulation, 94:1528-1536 (1996); and Akkerhuis et al., xe2x80x9cMinor Myocardial Damage and Prognosis: Are Spontaneous and Percutaneous Coronary Interventionxe2x80x94Related Events Different?xe2x80x9d Circulation, 105:554-556 (2002)). These biochemical markers include the enzyme creatine kinase (xe2x80x9cCKxe2x80x9d), the myocardial specific enzyme CKMB, and the myocardial cell protein troponin I and troponin T, and an increase in these markers after PCI is associated with a worsened prognosis.
The causes of myocardial enzyme elevation after otherwise successful PCI are multiple and are believed to include the development of mechanical complications such as slow flow, side branch occlusion, transient major vessel closure, or prolonged coronary spasm (Klein and Oh). In the majority of cases, however, enzyme release occurs without any apparent mechanical complication. In this setting, the most likely cause is microembolization (Topol et al., xe2x80x9cRecognition of Importance of Embolization in Atherosclerotic Vascular Disease,xe2x80x9d Circulation, 101:570-580 (2000)).
In an effort to reduce post-PCI complications, various compounds can be administered to the subject. These include glycoprotein IIb/IIIa receptor antagonists, aspirin, and heparin. However, these compounds have not proven to be wholly effective in reducing post-PCI myocardial necrosis and other forms of post-PCI cell myocardial cell damage.
Accordingly, there exists a need for methods of protecting against the incidence of myocardial necrosis and other forms of myocardial cell damage during or subsequent to PCI. The present invention is directed, in part, to meeting this need.
The present invention relates to a method for reducing myocardial cell damage during and/or after percutaneous coronary intervention in a subject""s coronary artery. The method includes instilling a beta blocker directly into the subject""s coronary artery prior to percutaneous coronary intervention.
The present invention also relates to a kit for carrying out percutaneous coronary intervention. The kit comprises a catheter and a beta blocker.